Double-Blinded Clinical Trials: A Gift from the Devil's Grandmother

By Thomas E. Serena MD, FACS, FACHM, FAPWCA

Editor's note:This blog post is part of the WoundSource Trending Topics series, bringing you insight into the latest clinical issues and advancement in wound management, with contributions by the WoundSource Editorial Advisory Board.

I do not know the origin of the phrase "...a gift from the devil's grandmother." I first read it in Einstein's letters to Schrödinger. Einstein employed the phrase to describe his fear of failing to find a unified theory of relativity and quantum physics. The problem appeared unsolvable.

A similar gift in the field of clinical trial research in wound healing appeared on my doorstep recently. I started my research career conducting double-blinded pharmaceutical trials. After a string of failures, I convinced myself that advanced therapy in chronic wounds was doomed; however, cellular and/or tissue-based products (CTPs) entered the market with encouraging results, brightening my spirits. To date, our cooperative group of investigators has published more than a dozen trials demonstrating the efficacy of CTPs in the treatment of diabetic and venous ulcers.

The Importance of Double-Blinded Trials

To conduct a randomized controlled clinical trial, we must study a homogenous population: for example, patients with diabetes with Wagner I or II ulcers, without renal failure and under adequate glucose control. On average, only about 10% of the wound clinic population qualifies for an RCT. A homogenous population allows an accurate comparison of an active treatment with standard of care. If the active agent heals more patients than standard of care, the product is said to be efficacious.

Want to read more about the population challenges involved in radomized controlled clinical trials? Click Here.

The difference between the earlier disappointing drug trials and the more recent CTP research comes down to blinding. Preventing the physicians and patients from knowing the active treatment dramatically reduces bias in a trial. No matter how conscientious the investigator, a tendency to favor the treatment arm undermines every unblinded investigation. Subconsciously, the investigator wants the treatment to work. Subtle favoring of the active treatment leads to less reliable results.

The Challenge of Clinical Trials in Wound Care

Incorporating a double-blind methodology into a pharmaceutical protocol is relatively simple: remove the active ingredient from the vehicle (e.g., gel), and use it as the placebo. Ah! But here is the fly in the grandmother's ointment: how does the gift apply to CTP trials? How do we blind them? I have discussed this issue with numerous physicians and scientists across the world. We can render a CTP inactive through techniques such as high-dose irradiation; however, the inactivated CTP placebo could injure patients. I continue to search for a harmless CTP look alike with weak biologic action.

CTP randomized clinical trials incorporating double blinding will carry more weight than unblinded trials, garner greater reimbursement, and give clinicians confidence that their patients will benefit from the pricey products.

About The Author
Dr. Thomas Serena has published more than 75 peer-reviewed papers and has made in excess of 200 presentations worldwide. He has been elected to the Board of Directors of both The Wound Healing Society and the American College of Hyperbaric Medicine (ACHM), the leading academic society in the field of Hyperbaric Medicine. In 2013 Dr. Serena was elected vice president of the American Professional Wound Care Association (APWCA) is currently the president-elect of the Association for the Advancement of Wound Care (AAWC). Dr. Serena has opened and operates Wound Care and hyperbaric oxygen treatment clinics across the United States.

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.